To prevent or reverse obesity and its ills, timing may be everything

If obesity is linked to Americans’ 24/7 lifestyles, would it help to reset the clock that dictates our eating? A new study of mice suggests it would, and in ways that go well beyond weight alone.

Even with a diet high in fat and sugar, mice that had their “eating day” compressed into a period of eight to nine hours and then fasted for the remainder of the day were less likely to become obese, says new research. Mice that observed a lengthy daily fast also suffered less systemic inflammation, fatty liver disease, worrisome cholesterol and metabolic disturbance than did mice that ate whenever they pleased.

The difference wasn’t how much or what the mice ate: Mice kept on a daily fasting regimen ate the same fattening chow, and just as much of it, as did those who were free to eat ‘round the clock. The only difference was when they ate it -- and how long they didn’t.

The daily fasters also showed exercise endurance far superior to that of mice who were allowed to eat whenever they wanted. They not only outran the chubby rodents allowed to eat all the fattening food they wanted, but they also left mice reared in normal, healthy chow in the dust.

Perhaps most exciting, mice that reaped the rewards of fasting could make an occasional dietary detour and still stay healthy. The latest research found the beneficial effects of a long daily fast during a five-day “workweek” can even withstand a regular departure from the strict regimen during a sequence of two-day “weekends.”

“I wouldn’t run out and start doing this in humans. Right now, we really don’t have the science to give those kinds of recommendations,” said physiologist Kenneth P. Wright, director of University of Colorado at Boulder’s sleep and chronobiology lab. “But this study is a tour de force, and studying these effects in humans is certainly the next step,” said Wright, who was not involved in the research.

The idea that timing one’s food consumption to maximize health is hardly new. Nutritionists have, until recently, insisted that breakfast is the most important meal of the day. But as research mounts on the ill effects of shift work and of chronic sleep deprivation, the idea that our cells also adhere to a sleep-wake cycle, and process fuel differently at different times of the day, has gained scientific currency. That, in turn, is prompting scientific interest in the notion that when we eat affects our well being as much as what we eat.

The latest study, by researchers at the Salk Institute for Biological Studies in La Jolla and published this week in the journal Cell Metabolism, fleshes out the limits and possibilities of using the clock to prevent or reduce obesity and to improve health. The group subjected 392 male lab mice, from the age of 12 weeks (the rough equivalent of early adulthood), to a variety of feeding patterns and gauged the effects of those patterns on a wide range of measures beyond weight gain, including body composition, metabolic function, inflammation, cholesterol levels and exercise endurance.

Compared with mice allowed to eat high-fat, high-sugar chow whenever they wanted, those given access to the same diet, but only for nine hours a day, gained only half as much weight, even though both groups consumed about the same number of calories.

When the researchers tested the effects of lengthening the window in which mice were allowed to feed on high-fat food, those maintained on a regimen of nine-hour feeding and 15-hour fasting gained the least weight. Mice allowed to eat the high-fat chow whenever they wanted gained 2 1/2 as much weight.

But even a moderate daily fast made a difference: Mice made to fast for only nine hours a day, and permitted to eat fat-laden chow for 15 hours, gained only 56% of weight that the all-day eaters had.

Although a long daily fast appeared to protect mice from becoming fat, it also aided in weight loss among mice who were obese. Obese mice switched from the eat-when-you-want mode to a 15-hour daily fast mode lost 5% to 12% of their body weight over three months, while the weigh of obese mice maintained on the eat-when-you-want diet continued to increase, between 10% and 25%.

The mice that adhered to daily fasts of 15 hours or more clearly laid down less fat -- probably because their bodies, once fasting, switched from using glucose for energy to burning fat. Inflammatory markers that play a key role in diabetes, heart disease and cancers were also tamped down, and the fasters’ livers were healthier.

Alas, lab mice are not humans. When it comes to eating, lab mice do not fall prey to late-night television advertisements that seduce with juicy cheeseburgers or chocolate shakes topped with turrets of whipped cream. They are not called upon to work, and eat, while others of their kind sleep. And they do not eat bowls of late-night ice cream while mourning a recent breakup.

They also do not, as do many modern-day Americans, live for the weekend. But in the Salk study, the health of daily fasters did suggest that brief weekly departures from their dietary norm might be forgiven.

In the current study, researchers switched mice who were well established on a long-daily-fast regimen to a weekly pattern of five days on followed by two days off. Despite the researcher-imposed weekend, these mice maintained their svelte shapes and their measures of good health.

Time-restricted feeding, say the authors, led by Salk scientist Satchidananda Panda, is a potentially powerful behavioral intervention that “de-emphasizes caloric intake, hence making it an attractive and easily adoptable lifestyle modification.” A large-scale randomized control trial would show whether the strategy would work in humans, they said.

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