Can timing of meals help with weight loss?

This is a story about the importance of good timing.

Excess weight contributes to a variety of health problems. Despite enormous effort over decades, the problem has proved extremely difficult to solve. Biologist Satchin Panda thinks we're missing a key variable: Instead of focusing so much on what we eat, he says, we should pay more attention to when we eat.

A researcher at the Salk Institute in San Diego, Panda argues that eating within a certain time window each day can help people lose weight and may help prevent illnesses including diabetes, heart disease and cancer. In animal studies, he and others have shown that limiting food intake to a period of eight to 12 hours can boost cognitive and physical performance, and may even lengthen life span. Known as time-restricted feeding, or TRF, the approach is simple: Eat more or less what you want, but don't consume anything before or after the allotted time.

Panda argues that humans' circadian rhythm is not designed for a world with 24-7 access to food. "If you're eating all the time, it messes up that pattern," he says. For many if not most Americans, that pattern is deeply out of whack, and many of us eat from early morning until late at night.

It is not clear whether TRF works in humans the way it seems to work in lab mice. For one, mice and humans have very different circadian rhythms. Mice are nocturnal and sleep more than once a day. They also live for only two or three years. "It may be that for a mouse, a 16-hour fast is the equivalent of a two- or three-day fast for a human," says Courtney Peterson, a nutrition scientist at the University of Alabama at Birmingham who is doing research on TRF in humans.

In addition, Peterson and others say, some of the benefits of TRF may stem from decreased consumption due to the shortened eating window: It's not really surprising that cutting out the after-dinner drink and the late-night sundae is good for weight loss and overall health. And, in fact, studies in humans and animals have found that TRF helps both mice and people eat fewer calories.

Panda first got interested in TRF 15 years ago, while studying the genetics of circadian rhythm. His research on mice revealed that over the course of a day, hundreds of liver genes turn on and off cyclically. The liver plays a central role in metabolising calories, and it turned out that most of these cyclic genes were involved in eating and digestion. This led him to ask whether mice - and humans, too - were programmed to eat according to a certain circadian schedule. In 2008, he began examining how mice responded to different feeding schedules; to his surprise, TRF had powerful health benefits.

The researchers compared two groups of mice, both of which consumed the same number of calories. One group was limited to an eight-hour window, while the other could eat at any time. After four months, the eight-hour mice weighed 28 percent less than the anytime eaters. "When we saw the results, they were so unexpected," he says. "Even I didn't believe it."

He had his students independently repeat the experiment three times; all of the results were similar. Using the same model - two groups eating an equal number of calories, but on different feeding schedules - he found that TRF mice had normal blood sugar levels, while the unlimited-schedule animals developed Type 2 diabetes. Since then, he has shown that TRF can reduce the risk of heart disease and cancer. In addition, mice restricted to an eight- or nine-hour eating window could run for twice as long as those that ate on a normal schedule.

"TRF is an interesting and valuable idea, but it's not proven that it works in humans," says nutrition researcher David Allison, dean of the University of Indiana School of Public Health. "There is some evidence to suggest that it might be useful for some things. But it's extraordinarily complex to actually nail this down."

Overall, he says, the evidence indicates that eating most of your food earlier in the day is probably healthier than eating most of your food later in the day. He also notes that there are many complexities to the issue, including the fact that most people eat healthier food at breakfast (oatmeal or cereal, for instance) than they do at dinner (hamburger, fries and dessert).

Some evidence from research involving humans indicates that TRF has benefits even when people don't eat any less. In a study that is soon to be published, Peterson examined eight men with pre-diabetes, a condition in which people are close to being diabetic but not quite there. Researchers prepared all food in the study, and the participants ate it under supervision. The men tried two schedules: eating all their meals between 8 a.m. and 2 p.m., and between 8 a.m. and 8 p.m. Compared with the 12-hour schedule, the six-hour window significantly lowered blood pressure and improved insulin sensitivity, the ability to process glucose.

"We were really excited about the results," Peterson says. "It was a small study, but it was done extremely carefully." In a similar study, also not yet published, she looked at 11 overweight people who followed the same two regimens. Although those in the six-hour window did not increase the overall number of calories they burned, they did increase the amount of fat they burned and reduced levels of a key hunger hormone called ghrelin; these metabolic changes might make it easier to lose weight and body fat.

"I think that within 10 years we will have some really clear guidelines for meal timing," Peterson says. "But we are in the early stages of this research. There is a lot more work we need to do."

In 2015, Panda looked at the eating patterns of 156 adults; more than half spread food consumption over 15 hours or longer, while only 10 percent consistently ate within a 12-hour window. He followed up with eight of these people, who were overweight and typically ate for 14 hours or more a day. When the subjects were limited to a 10-hour window for four months, with no other restrictions - they could eat whatever they wanted - they lost weight, slept better and had more energy.

Panda is now starting a study that will eventually include thousands of adults worldwide. Using a custom smartphone app that allows people to take photos of what they eat and immediately send them to researchers, he will be able to more accurately track which foods people eat. Using this data, he will examine whether TRF can improve weight, blood sugar, blood pressure, joint pain, sleep, anxiety and inflammation.

Panda says that mice and humans - and probably most organisms - are not built to simultaneously ingest food and metabolise it. "Everything cannot happen at once," Panda says. "The body can't take in calories and break down calories at the same time." He and other circadian scientists say that many if not most animals have evolved to consume food according to the 24-hour solar cycle. For humans, this rhythm involves eating during the day and sleeping after sunset. With the advent of electric lights, refrigerators, microwaves and 7-Elevens, millions if not billions of us have jettisoned this pattern. But the circadian rhythm of our metabolism still expects us to stop eating at sundown. This mismatch between modern society and programmed biology can lead to myriad health problems, Panda and others say.

It is not clear exactly how TRF works, but it seems to trigger several molecular changes. It increases the activity of mitochondria, which provide energy to cells throughout the body; it boosts levels of ketone bodies, molecules produced by the liver during fasting, which are a powerful source of energy and are especially useful to muscle and brain cells; it also raises production of brown fat, the "good" fat that helps the body burn more energy. Together, these mechanisms allow the body to generate more energy and metabolise calories more efficiently than unscheduled eating.

TRF is just one of several approaches that involve fasting. Scientists are also looking at intermittent fasting, which typically involves eating every other day, or eating for five days and then fasting for two.

Valter Longo, a gerontologist at the Longevity Institute at the University of Southern California, has focused on an approach in which people eat very little for five days at a time, several times a year. Other researchers are examining calorie restriction, which requires reducing calorie intake below normal levels, for months, years or longer, in hopes of triggering a variety of beneficial physiological responses. Studies of animals and humans have found that these regimens can have benefits, including weight loss, lower rates of cancer, diabetes and heart disease, and, in some animal studies, significantly longer life span.

All of these strategies have some similarities to TRF, Panda says, with one major difference: They are much more difficult to follow. Whereas TRF involves relatively minor adjustments in how most people already eat, intermittent fasting and calorie restriction often require hunger and discipline for long periods.

This, he says, is why TRF has potential as a public health strategy. In a society where Big Gulps and Big Macs are ubiquitous, unhealthy eating and obesity are very hard to avoid. TRF, Panda contends, offers a simple, relatively manageable alternative. "Just by changing when we eat, we can have an effect on obesity and these related problems," Panda says. "This can really move the needle."

Panda himself has adopted TRF and says he's seen benefits: lower blood sugar, weight loss, better sleep and more energy. He now uses a modified version, in which he eats breakfast at 7 a.m., skips lunch and has dinner with his family at around 7 p.m. In essence, he has two long fasts a day, between meals and overnight. Others around him have adopted the classic TRF regimen, including his 15-year-old daughter, his mother and several graduate students in his lab. He says his mother had pre-diabetes before starting the diet; since then, her blood sugar has dropped significantly, to a healthy level.

So far, TRF has not caught on widely. Peterson, the UAB scientist, is one of the early adopters. Five to seven days a week, she limits her consumption to a six- or seven-hour window, usually eating between 8 a.m. and 2 or 3 p.m. She says she has more energy, feels a bit calmer and doesn't feel particularly hungry in the afternoon or evening.

"You have to adapt to it," she says. "When I first started trying this, I found 10 hours was hard. Now, six hours seems easy."