Intermittent fasting and why when you eat makes a difference

But there is more to rising obesity rates than endless grazing. What also matters is timing, some experts believe. We eat when we shouldn’t, and don’t give our bodies a long enough break in between.

We didn’t evolve to eat day and night, says neuroscientist Dominic D’Agostino of the University of South Florida. Until the dawn of agriculture about 12,000 years ago, we subsisted on hunting and gathering and often had to perform those activities with empty bellies. “We are hard-wired,” D’Agostino says, “to undergo periodic intermittent fasting.”

What’s more, people are now eating at times of the day when historically they would have been asleep, says Satchin Panda, a circadian biologist at the Salk Institute for Biological Studies in La Jolla, Calif., who co-wrote an overview on the timing of eating in the 2019 Annual Review of Nutrition. For thousands of years, he says, our nightly fast probably started much earlier than in these times of late-night television. 

Although the research is still mixed, the timing of eating seems to matter for body weight and health. Studies suggest significant potential benefits from fasting every other day or so — or, on a daily basis, eating only when we would normally be awake, within a window of 12 hours or fewer — a practice known as time-restricted eating.

Such practices — referred to under the umbrella term “intermittent fasting” — may help ward off obesity. More speculatively, there are signs in animal studies that the regimens might enhance athletic endurance and cognition, alleviate diabetes and perhaps even help combat other medical conditions.

How Americans became a nation of snackers is complicated, but part of the problem is studies starting in the 1960s that found apparent benefits from eating many small, nutritious meals throughout the day. Nibbling advice became a health mantra, partly based on the belief that frequent eating revs up the metabolism and makes the body burn more calories. This could be one of the reasons “lots of people are now eating for 16 hours a day,” says biochemist Valter Longo of the University of Southern California.

Newer human research finds no support for the notion that endless nibbling increases metabolic rate, says Antonio Paoli of the University of Padua in Italy. One 2017 study found that people who ate three or more times per day gained more weight per year than those eating just one or two meals per day.

So could breaks between meals actually be good for one’s health?  Studies as far back as the 1940s  reported that regimens akin to intermittent fasting improved health and prolonged life span in animals like rats. But it was unclear whether this was because of the breaks or simply because the animals consumed fewer calories.

One of the first hints that pauses in eating might be healthy came from a 2003 mouse study led by neuroscientist Mark Mattson, at that time at the National Institute on Aging. He and his colleagues compared a group of mice fed every other day with mice fed every day. Those groups ate essentially the same amount of food overall. Researchers also followed another group, which ate 40 percent less.

After 20 weeks, the mice in the first two groups weighed about the same. But, strikingly, both the alternate-day-fasting mice and the fewer-calories group were healthier (including lower blood sugar and insulin levels), than the daily eaters.

The study also suggested that intermittent fasting might improve brain function, which from an evolutionary perspective makes sense, says Mattson, now at Johns Hopkins University School of Medicine. After all, when an animal is in a state of hunger, it needs the brain to stay sharp so it can find food.

Studies to replicate Mattson’s animal findings in people are difficult, however. Trials in which people eat less or nothing every other day, or every few days, consistently do show weight loss and improved cardiovascular health. But you can get similar results simply by cutting calories. It has been hard to prove that the periodic breaks from eating have added benefits.

In the longest human trial reported so far, nutrition researcher Krista Varady of the University of Illinois at Chicago and her team randomly assigned 100 otherwise healthy obese people to one of three groups: Group one ate just 25 percent of their normal intake every other day (and 25 percent more than normal on days in between); group two ate 75 percent of their calorie needs every day; and group three ate normally.

The study, published in 2017, found that both groups one and two lost the same amount of body weight on average (about 7 percent) and displayed similar measures for risk factors for heart disease and diabetes. That the intermittent fasting offered no additional benefits beyond traditional calorie restriction was “pretty disappointing,” says nutrition scientist Courtney Peterson from the University of Alabama at Birmingham.

Meanwhile, another strand of research suggested that the timing of meals also matters for health. A rodent study in 2009, led by sleep researcher Fred Turek at Northwestern University, showed that mice fed a high-calorie diet during the day (when the nocturnal animals would normally be asleep) gained a lot more weight than mice fed the same diet during the night, even though the animals consumed the same number of calories.

The same year, neuroscientist Frank Scheer of Brigham and Women’s Hospital and a professor at Harvard Medical School, reported that putting people on an artificial, 28-hour “day” in a lab for 10 days (so that they often ate at times when they would normally be sleeping) led to increased blood pressure and levels of blood sugar and insulin. “That,” Peterson says, “was a huge watershed study because it showed, literally, that the time when you eat affects your health.”

If eating when the body should be sleeping is unhealthy, then it follows that restricting eating to waking hours might be healthy. That’s what Panda’s team showed in studies published in 2012 and 2014. They reported that mice fed a calorie-dense diet during windows of eight to 12 hours at night (the animals’ active time) were protected from becoming obese and gained less weight than mice able to eat at any time — even though both groups ate the same number of calories.

Restricting eating to just nine hours at night even caused obese mice to lose weight. It also lowered their blood sugar and improved glucose tolerance, suggesting that time-restricted eating might help alleviate diabetes.

It’s unclear, though, whether Panda’s mouse findings apply to people — mice studies often don’t translate to humans. “It sounds too good to be true,” says research dietitian Michelle Harvie of Manchester University NHS Foundation Trust in the United Kingdom.  One human study published in 2007, she says, even suggested that restricting eating times too much can be bad. When people ate all their calories in a single meal between 4 and 8 p.m., blood sugar levels rose, and glucose tolerance worsened, both signs of ill health.

A recent, randomized, controlled study in overweight and obese people also showed no improvement from restricting eating times to the eight hours between noon and 8 p.m.

Still, some researchers think the problem with such disappointments might lie in timing. Peterson suspects that in both these studies, the last daily meal might have been consumed too late, when blood insulin levels had dropped too low to process food properly.

In 2018, Peterson and her colleagues reported lower blood pressure and better-controlled blood sugar levels in eight overweight prediabetic men asked to eat all their food within a six-hour window — but with dinner before 3 p.m. If confirmed with more people, the study would indicate that restricting eating to a window of less than 12 hours while we are awake can have health benefits independent of calorie reduction, as long as the window isn’t too late in the day.

And what’s going on in the body to make it healthier to eat at one time than another? Daily biological rhythms may be central here, says Dorothy Sears, an obesity researcher at Arizona State University. It’s during the day that your body is best able to process food, says Sears, who wrote about the metabolic effects of intermittent fasting in the 2017 Annual Review of Nutrition. And just as the brain needs rest at night to do much-needed repair and cleanup work, so does the body, Panda says.

All the unsettled points and lack of clear-cut evidence from human trials hasn’t stopped thousands of enthusiasts from experimenting with their own personal intermittent-fasting regimens, in large part because many find it easier to count hours than calories. And there’s hope it might become easier still, if what goes for mice goes for people: Panda’s rodent studies suggest that skipping weekends doesn’t ruin the time-restricted health effect.

“You think, ‘What about Saturday night, when I go out for a late dinner?’ In the mice, that is okay,” Sears says. “It’s very encouraging, because it seems that you don’t have to ask people to be perfect every day of the week. . . . And you don’t ever have to read a label.”

Andreas von Bubnoff is a freelance science writer and professor of science communication based in Germany. He drinks his morning latte in a beer mug and likes to have breakfast at noon. This article was first published in longer form in Knowable Magazine.

The data is not all in, but here’s how a few of the scientists who study intermittent fasting incorporate what they have learned into their own lives:

●Satchin Panda, circadian biologist at the Salk Institute for Biological Studies in La Jolla, Calif., fasts for 14 hours every night and eats only twice a day: breakfast, and then dinner before 6 p.m. In general, he recommends not eating for an hour or two after waking up, and for three hours before going to bed. 

●Dominic D’Agostino, neuroscientist at the University of South Florida, follows a low-carb ketogenic diet and doesn’t eat until noon or midafternoon — except for a glass of water with lemon and black coffee — on days with important work, to enhance his focus. “I feel sharper, more creative in that state,” he says.

●Mark Mattson, a Johns Hopkins University neuroscientist, fasts for about 18 hours every night: He eats only after a late-morning exercise session. He says it takes about a month to adjust to such a regimen without getting hungry.

●Valter Longo, a University of Southern California biochemist, has developed (and occasionally follows) a “fasting-mimicking diet” intended to be eaten for five consecutive days. Other than that, Longo says to look to the habits of certain centenarians who follow low-meat diets and regularly avoid eating for 12-hour stretches. “You really don’t see centenarians fasting for 16 hours a day,” he says.