March 31, 20259 min readDoes Intermittent Fasting ImproveHealthBeyond Weight Loss?Intermittent fasting has gained a following, in part because of tantalizing hints that it can boost cognition, fend off cancer and even slow agingBy Nic Fleming & Nature magazine TanyaJoy/Getty ImagesAs anyone seeking to lose weight knows, diets come in and out of fashion. The Sexy Pineapple diet, launched by a Danish psychologist in 1970, never really took off. Kelloggs no longer promotes the Special K diet, which swaps out two meals a day for a bowl of the breakfast cereal of that name. These days, you dont hear much about eating according to blood type, cutting out acidic foods or following the potato diet.Intermittent fasting has, however, had unusual staying power for more than a decadeand has grown even more popular in the past few years. One survey found that almost one in eight adults in the United States had tried it in 2023.The enduring popularity of intermittent fasting has been fed by celebrity endorsements, news coverage and a growing number of books, including several written by researchers in the field. More than 100 clinical trials in the past decade suggest that it is an effective strategy for weight loss. And weight loss generally comes with related health improvements, including a reduced risk of heart disease and diabetes. What is less clear is whether there are distinct benefits that come from limiting food intake to particular windows of time. Does it protect against neurodegenerative diseases such as Alzheimers disease, enhance cognitive function, suppress tumours and even extend lifespan? Or are there no benefits apart from those related to cutting back on calories? And what are the potential risks?On supporting science journalismIf you're enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today.Neuroscientist Mark Mattson at the Johns Hopkins School of Medicine in Baltimore, Maryland, and author of the 2022 book The Intermittent Fasting Revolution, has been studying fasting for 30 years. He argues that, because ancient humans went for long periods without food as hunter-gatherers, we have evolved to benefit from taking breaks from eating. Were adapted to function very well, perhaps optimally, in a fasted state, he says.Fastings deep rootsFasting is far from new. Periodic abstentions from food have long been practised in many religions. In the fifth century bc, the Greek physician and philosopher Hippocrates prescribed it for a range of medical conditions.Recent scientific interest in fasting has its roots in questions raised by research on calorie restriction. Since the 1930s, studies have shown that putting rodents on low-calorie diets can increase their lifespans. Hypotheses proposed to explain this effect include that calorie restriction slows growth, lowers fat intake or reduces cellular damage caused by unstable free radicals.But an observation made in 1990 by researcher Ronald Hart, who was then studying ageing, nutrition and health at the US National Center for Toxicological Research in Jefferson, Arkansas, highlighted another intriguing possibility. Calorie-restricted rodents fed once daily consumed all their food in a few hours. Perhaps the calorie-restricted rodents lived longer because they repeatedly went for 20 or so hours without eating.In the immediate aftermath of a meal, cells use glucose from carbohydrates in food as fuel, either straight away or following storage in the liver and muscles as glycogen. Once these sources are depletedin humans, typically around 12 hours after the last mealthe body enters a fasted state during which fat stored in adipose tissue is converted to ketone bodies for use as an alternative energy source.Intermittent fasting generally refers to various diets that include repeated periods of zero- or very low-calorie intake that are long enough to stimulate the production of ketone bodies. The most common are time-restricted eating (TRE), which involves consuming all food in a 4- to 12-hour window, usually without calorie counting; alternate-day fasting (ADF), whereby people either abstain from food every other day or eat no more than around 500 calories on that day; and the 5:2 diet, which stipulates a 500-calorie limit on 2 days per week (see Three forms of fasting).Some researchers say the resulting shift between sources of energy, called metabolic switching, triggers key adaptive stress responses, including increased DNA repair and the breakdown and recycling of defective cellular components. Those responses, the thinking goes, provide health benefits beyond those from reduced calorie consumption alone. Observational studies have suggested that some religious fasters who fast long enough for metabolic switching to occur see such health benefits, although these studies have a lot of limitations.Getting slim fastControlled diet trials are notoriously difficult to conduct. Peoples diets and behaviours, together with their genetic inheritance and baseline health, make for a lot of variables. Often, people dont stick with the study, and getting participants to track calorie intake accurately is a known challenge.Still, the weight of the evidence suggests that intermittent fasting can help people to lose weight. In 2022, for example, Courtney Peterson, who researches nutrition at the University of Alabama at Birmingham, and her colleagues reported results from a trial involving 90 adults with obesity who also received counselling to help them lose weight. She found that those who followed TRE for an average of 6 days per week over 14 weeks lost an average of 6.3 kilograms, compared with the 4 kg lost by participants who ate over 12 or more hours. Peterson says that many people find following a rule about when to eat and when not to eat easier than counting calories or eating healthier. We and others have found that TRE also makes people less hungry, so they tend to naturally eat less and lose weight, says Peterson.Also in 2022, nutritionist Krista Varady at the University of Illinois, Chicago, and her colleagues reviewed 22 randomized trials looking at the effects of ADF, the 5:2 diet and TRE on body weight. ADF and the 5:2 diet produced 48% weight loss after 812 weeks in those with obesity, whereas TRE helped people to lose 34% of their body weight over the same period.Varady has a long-standing interest in fasting. The cover of one version of her 2013 book The Every Other Day Diet features pizza, a doughnut and a burger to illustrate that those doing ADF dont need to cut out unhealthy foods. In the book, Varady argues that restricting intake to no more than 500 calories every other day is a more effective way to lose weight than conventional calorie counting and cutting out fatty and sugary foods.Although most researchers who study intermittent fasting agree that it can help people to lose weight, theyre split on whether there are any benefits beyond those that come from simply eating less. Michelle Harvie, a research dietitian at the University of Manchester, UK, sought to address this question in collaboration with Mattson in a 2010 trial. They found that overweight women who followed a 5:2 diet for 6 months had larger reductions in fasting insulin and insulin resistance than did those on a reduced-calorie diet. Both groups had the same weekly calorie intake and lost an average of around 6 kg. But the difference in insulin levels was small, and the researchers relied on participants to track consumption by keeping food diaries.In a 2018 study, Peterson and her team carefully monitored the diets of prediabetic, overweight men, matching their diets to energy consumption. The participants ate all their food either within 6 hours before 3 p.m. daily, or over 12 hours, for 5 weeks before switching to the other eating schedule. Although both regimes resulted in equivalent small weight loss over the study period, when men were on the more time-restricted diet, they had improved insulin sensitivity, lower blood pressure and reduced oxidative stress, a form of molecular damage.We showed for the first time that intermittent fasting has health benefits and effects beyond weight loss in humans, says Peterson. But the study was relatively small: only 12 adults started the trial, only 8 completed it, and all were male and overweight.Adding to the uncertainty is that other trials have reached seemingly contradictory conclusions. Nisa Maruthur, a physician at the Johns Hopkins School of Medicine, and her colleagues asked 41 obese adults with pre-diabetes or diabetes to consume diets that matched their energy needs, eating either during a 10-hour daily window or according to their normal schedule. After 12 weeks, there was little difference between the two groups in the average changes to weight, glucose regulation, blood pressure, waist circumference or lipid levels. Weight loss seen in prior studies of TRE was probably the result of eating fewer calories, says Maruthur, whose study was published in 2024. If so, metabolic switching might not come with added health benefits.Peterson, a co-author of that study, disagrees and suggests that the 10-hour eating window might have been too long to achieve the results seen in trials of shorter TRE windows.Even though Varady thinks that intermittent fasting can help people to lose weight, she remains unconvinced that it has effects independent of calorie restriction. Based on current human evidence, I dont think that there are any benefits of intermittent fasting beyond weight loss, she says.Mattson is equally sure of the opposite: There is considerable evidence of benefits of intermittent fasting that cannot be explained by reduction in calorie intake.Mattson and others have looked to animal research in their efforts to understand the physiology of fasting, and to identify mechanisms that could underpin any extra health benefits.Beyond the waistlineAs early as 1999, Mattson and his team began finding evidence that ADF protects rodents against damage linked to neurodegenerative diseases and acute brain injuries such as stroke. Fasting has been shown to increase production of -hydroxybutyrate, a ketone body that protects neurons from damage in rodent models of Alzheimers and Parkinsons disease. Studies in rodents show that intermittent fasting can improve cognitive functions, such as working memory, spatial learning and memory retention. It can also reduce tumour occurrence as the animals age and increase their sensitivity to chemotherapy.Other results have come from Satchin Pandas lab at the Salk Institute for Biological Studies in La Jolla, California. Panda became interested in fasting almost by accident, through his research on circadian rhythms. In a series of experiments beginning in 2009, he and his team found that changing the feeding times of mice had more effect than light cycles did on circadian rhythms in liver gene expression. When mice on high-fat diets were restricted to feeding during eight hours at night (the natural feeding time of mice), they were protected from obesity, elevated insulin levels, fatty liver disease and inflammation, compared with mice that ate the same number of calories but fed whenever they wanted during both day and night.I realized these mice didnt have diet-induced obesity as others had concluded; rather, they had circadian-rhythm-disruption-induced obesity, says Panda.Eating in time with circadian rhythms also seems to affect longevity in mice. In a 2022 study, neurobiologist Joseph Takahashi at the University of Texas Southwestern Medical Center in Dallas, and his colleagues reported that whereas calorie-restricted mice that fed during the day lived 20% longer than did controls that fed as much as they liked, those on calorie-restricted diets fed at night lived 35% longer, on average.There are hints of a circadian effect in humans, too. In a 2024 review of TRE trials, Peterson found that study participants who ate before 6 p.m. had improved blood-sugar and insulin control, but she did not see the same effect in those who adopted later eating windows. Most peoples blood-sugar control is best in the mid- to late morning, so eating early, in alignment with these circadian rhythms, results in lower overall blood-sugar levels, she says.Research into the physiology of intermittent fasting also suggests that its effects might not be simply a function of calorie restriction. Stem-cell biologist mer Yilmaz at the Massachusetts Institute of Technology in Cambridge, and his colleagues have shown how stem-cell activity increases in the intestines of both calorie-restricted and fasted micean effect triggered by the breakdown of fatty acids. Both caloric restriction and fasting improved intestinal stem-cell activity and health, but the mechanisms involved are very different, he says. If the mechanisms are different, the health implications might vary, too.The work in animals also points to possible downsides of fasting. Because intestinal stem cells can divide frequently, they are a source of precancerous cells. In mice with cancer-gene mutations, there was more tumour development in those that fasted and then ate for a day than in mice that did not fast, Yilmaz and his colleagues reported in 2024. Other animal work suggests that long fasts could blunt immune responses.Researchers say there needs to be more work to understand the implications of animal experiments for humans. For now, doctors caution that fasting could cause blood-sugar levels to drop dangerously in those with diabetes; affect milk supply in people who are breastfeeding; harm growth in children; and increase the risk of complications for those on blood-pressure and heart-disease medications.Although researchers remain intrigued by the physiology of fasting, would-be dieters probably care more about whether intermittent fasting works than why it does so. In her job as a primary-care physician, Maruthur advises people to try it even though she thinks its effects are entirely the result of eating less.If you restrict the window of time in which you eat, then youre likely to consume less, she says. If youre the kind of person whos going to eat fewer calories as a result, it might be worth giving it a go.This article is reproduced with permission and was first published on March 25, 2025.