Time-restricted eating can overcome the bad effects of faulty genes and unhealthy diet

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Time-restricted eating can overcome the bad effects of faulty genes and unhealthy diet

Everything in our body is programmed to run on a 24-hour or circadian time table that repeats every day. Nearly a dozen different genes work together to produce this 24-hour circadian cycle. These clocks are present in all of our organs, tissues and even in every cell. These internal clocks tell us when to sleep, eat, be physically active and fight diseases. As long as this internal timing system work well and we obey them, we stay healthy.

But what happens when our clocks are broken or begin to malfunction?

Mice that lack critical clock genes are clueless about when to do their daily tasks; they eat randomly during day and night and succumb to obesity, metabolic disease, chronic inflammation and many more diseases.

Even in humans, genetic studies point to several gene mutations that compromise our circadian clocks and make us prone to an array of diseases from obesity to cancer. When these faulty clock genes are combined with an unhealthy diet, the risks and severity of these diseases skyrocket.

My lab studies how circadian clocks work and how they readjust when we fly from one time zone to another or when we switch between day and night shift. We knew that the first meal of the day synchronizes our circadian clock to our daily routine. So, we wanted to learn more about timing of meals and the implications for health.

Time-restricted eating

Chicken clock UC San Diego
Eating within an eight- to 12-hour window could diminish the impact of a bad diet and a broken body clock.
Credit: amornchaijj/Shutterstock.com

A few years ago we made a surprising discovery that when mice are allowed to eat within a consistent eight- to 12-hour period without reducing their daily caloric intake, they remain healthy and do not succumb to diseases even when they are fed unhealthy food rich in sugar or fat.

The benefit surpasses any modern medicine. Such an eating pattern – popularly called time restricted eating – also helps overweight and obese humans reduce body weight and lower their risk for many chronic diseases.

Decades of research had taught us what and how much we eat matters. But the new discovery about when we eat matters raised many questions.

How does simply restricting your eating times alter so many elements of personal health? The timing of eating is like an external time cue that signals the internal circadian clock to keep a balance between nourishment and repair. During the eating period, metabolism was geared toward nourishment. The gut and liver better absorbed nutrients from food, and used some for fueling the body while storing the rest.

During the fasting period, metabolism switched to rejuvenation. Unwanted chemicals were broken down, stored fat was burned and damaged cells were repaired. The next day, after the first bite, the switch flipped from rejuvenation to nourishment. This rhythm continued every day. We thought that timing of eating and fasting was giving cues to the internal clock and the clock was flipping the switch between nourishment and rejuvenation every day. However, it was not clear if a normal circadian clock was necessary to mediate the benefits of time restricted eating or whether just restricted eating times alone could flip the daily switch.

Man in chair eating pizza at night
Eating late at night can disrupt circadian rhythms and raise the risk of chronic diseases including obesity.
Credit: Ulza/Shutterstock.com

What if you have a broken internal clock?

In a new study, we took genetically engineered animals that lacked a functioning circadian clock either in the liver or in every cell of the body.

These mice, with faulty clocks don’t know when to eat and when to stay away from food. So, they eat randomly and develop multiple diseases. The disease severity increases if they are fed an unhealthy diet.

To test if time restricted eating works with a damaged or dysfunctional clock, we simply divided these mutant mice into two different groups – one group got to eat whenever they wanted and the other group was only given access to food during restricted times. Both groups ate the identical number of calories, but the restricted eaters finished their daily ration within nine to 10 hours.

We thought that even though these mice had restricted eating times, having the bad clock gene would doom them to obesity and many metabolic diseases. But to our utter surprise the restricted eating times trumped the bad effects of faulty clock genes. The mice without a functioning clock that were destined to be morbidly sick, were as healthy as normal mice when they consumed food during a certain period.

The results have many implications for human health.

The good news

First of all, it raises a big question: What is the connection between our genetically encoded circadian clock timing system and external time of eating? Do these two different timing systems work together like co-pilots in a plane, so that even if one is incapacitated, the other one can still fly the plane?

Deep analyses of mice in our experiment revealed that time restricted eating triggers many internal programs that improve our body’s resilience — enabling us to fight off any unhealthy consequences of bad nutrition or any other stress. This boost in internal resilience may be the key to these surprising health benefits.

Man in chair eating pizza at night
As we age, our body clocks become less accurate, and we become more prone to chronic diseases. Keeping regular, restricted eating times can keep us healthy longer.
Credit: LightField Studios/Shutterstock.com

For human health the message is simple, as I say in my new book “The Circadian Code.” Even if we have faulty circadian genes as in many congenital diseases, such as Prader-Willi syndrome or Smith-Magenis syndrome, or carry a malfunctioning copy of nearly a dozen different clock genes, as long as we have some discipline and restrict eating times, we can still fend off the bad effects of bad genes.

Similarly, other researchers have shown as we get older our circadian clock system weakens. The genes don’t function correctly so our sleep-wake cycles are disrupted — just as if we had a faulty clock. So, lifestyle becomes more important for older people who are at higher risk for many chronic diseases such as diabetes, heart disease, high cholesterol, fatty liver disease and cancer.

As a potential translation to human health, we have created a website where anyone from anywhere in the world can sign up for an academic study and download a free app called MyCircadianClock and start self-monitoring the timing of eating and sleeping.

Diagram of clock app
Research has shown that our daily eating, sleeping and activity patterns can affect health and determine our long-term risk for various diseases. This app is part of a research project that uses smartphones to advance research into biological rhythms in the real world, while also helping you understand your body’s rhythms.
Credit: http://mycircadianclock.org/#about-studyCC BY-SA

The app provides tips and guidance on how to adopt a time restricted eating lifestyle to improve health and prevent or manage chronic diseases. By collecting data from people with varying risk for disease, we can explore how eating times can help to increase our healthy lifespan.

We understand everyone’s lifestyle around home, work and other responsibilities is unique and one size may not fit all. So, we hope people can use the app and some tips to build their personalized circadian routine. By selecting their own time window of eight to 12 hours for eating that best fits their lifestyle, they may reap many health benefits.

 

 

This article was originally published in NIH. Read the original article.

Which Kinds of Foods Make Us Fat?

Which Kinds of Foods Make Us Fat?

One fundamental and unanswered question in obesity research is what kind of foods contribute most to the condition. Experts variously blame, for example, fatty or sugary fare or foods that lack protein, which may prompt us, unconsciously, to overeat. Plenty of anecdotal evidence can be marshaled against any of the culprits, but there has been little long-term, large-scale experimental research on people’s comparative eating habits. It is neither ethical nor practical to have healthy subjects gorge themselves on one diet for years until they are obese.

It is possible, though, to conduct this sort of experiment on mice. For a diet study published this summer in Cell Metabolism, researchers randomly assigned one of 29 different diets to hundreds of adult male mice. (The scientists hope to include female mice in later experiments.) Some diets supplied up to 80 percent of their calories in the form of saturated and unsaturated fats, with few carbohydrates; others included little fat and consisted largely of refined carbohydrates, mostly from grains and corn syrup, although in some variations the carbs came from sugar. Yet other diets were characterized by extremely high or low percentages of protein. The mice stayed on the same diet for three months — estimated to be the equivalent of roughly nine human years — while being allowed to eat and move about their cages at will. The mice were then measured by weight and body composition, and their brain tissue was examined for evidence of altered gene activity.

Only some of the mice became obese — almost every one of which had been on a high-fat diet. These mice showed signs of changes in the activity of certain genes too, in areas of the brain related to processing rewards; fatty kibble made them happy, apparently. None of the other diets, including those rich in sugar, led to significant weight gain or changed gene expression in the same way. Even super-high-fat diets, consisting of more than 60 percent fat, did not lead to significant weight gains, and the mice on those diets consumed less food over all than their counterparts, presumably because they simply could not stomach so much fat. These findings were replicated in subsequent experiments with four other murine breeds. Male mice on relatively high fat diets became obese. The others did not.

“It looks like consuming high-fat diets, if they aren’t extremely high fat, leads to weight gain, if you are a mouse,” says John Speakman, a professor at the Chinese Academy of Sciences in Beijing and at the University of Aberdeen in Scotland, who oversaw the study. Speakman and his co-authors believe that the fatty meals stimulated and altered parts of the brains, causing the mice to want fatty food so much that they ignored other bodily signals indicating that they had already consumed enough energy.

The study was focused on weight gain, not loss, and its subjects were mice, of course, not humans. But the results are suggestive. Sugar did not make the mice fat, and neither did protein deficits. Only fat made them fat.

 

This article was originally published in The New York Times.  Read the original article.

In a Hurry? Try Express Weight Training

In a Hurry? Try Express Weight Training

Here’s some good news for anyone who does not have the time or inclination to linger in the gym and grunt through repeated, hourslong sets of various weight-training exercises in order to build muscular strength.

An inspiring new study of how much — or little — weight training is needed to improve muscles’ strength and size finds that we may be able to gain almost the same muscular benefits with a single, brief set of each exercise.

The catch is, that set has to be draining.

A set is a given number of repetitions of an individual exercise, whether that move is a bench press or biceps curl.

In general, we are advised to complete eight to 12 repetitions of an exercise during a set, with the aim of making our working muscle so tired by the end of the set that we temporarily cannot complete another repetition.

This process is known, almost poetically, as lifting to failure.

Most of us who lift weights probably have heard that, if we hope to gain size, strength and endurance in our muscles, we should aim to complete at least three sets of each exercise during a full session, meaning that we would be expending considerable sweat and time at the gym.

But there has been surprisingly little definitive science to support these notions, and much of the available research had focused on people who were new to the sport and whose muscles tend to respond vigorously to any amount of this unfamiliar activity.

Whether they and the rest of us would need to add more sets and effort once we had become accustomed to weight training if we hoped to keep augmenting our strength was not clear.

So, for the new study, which was published in August in Medicine & Science in Sports & Exercise, researchers at Lehman College in the Bronx and other institutions decided to test just how much weight training is required to continually make muscles larger and stronger.

Their first step was to recruit 34 fit young men who were not burly weight lifters but did resistance train with some regularity.

The researchers tested these men’s current muscular strength, endurance and size and then randomly assigned them to one of three different supervised weight-training routines.

The general program was simple and familiar, consisting of seven common exercises, including the bench press, lateral pull-down, machine leg press and others. A set of any of these exercises would require lifting to failure through eight to 12 repetitions.

But the “dose” of the exercises assigned to each group differed.

One group was asked to complete five sets of each exercise, with about 90 seconds of rest between sets. Their total time for a session at the gym was almost 70 minutes.

A second group was asked to complete three sets of each exercise, requiring they work out for about 40 minutes.

The third group had to finish only one set of each exercise, meaning that they were done after a brisk 13 minutes.

Each volunteer performed his given workout three times a week for eight weeks and then returned to the lab to repeat the muscle measurements.

After the two months, all of the young men were stronger, a finding that, by itself, is beguiling, since it suggests that people can continue to gain strength even if they already are experienced at resistance training.

But more interesting and surprising, the strength improvements were essentially the same, no matter how many — or few — sets the men completed.

The men who had stopped after one set gained as much strength as those who had done five sets or three.

The groups likewise showed equivalent improvements in muscular endurance, which was measured by how any times they could repeat a bench press exercise, using a low weight.

Only the size of the men’s muscles differed. Those who had completed five sets per session sported greater muscle mass than those who had done three sets or one.

But they were not noticeably stronger.

These results suggest that “there is a separation between muscular strength and hypertrophy,” or enlargement of the muscle, says Brad Schoenfeld, the director of the human performance program at Lehman College and the study’s lead author.

Your muscles can become as strong as those of someone who is burlier.

You also probably can gain this strength with one set of lifts, he says; five and even three sets were not necessary in this study to improve strength.

What was required was to strain the working muscles to limp exhaustion by the end of each set, he says. In effect, you should be physically unable to complete another repetition at that point, without resting.

“A lot of people probably do not push themselves that much” during a session at the gym, he says. “You have to reach failure” during a set for the training to succeed.

If you are new to resistance training or worried about injuring yourself, you may want to consult a trainer about proper form and how to determine the right weight for you to be lifting, he says.

Of course, this study was short term and involved young men, so we cannot know whether the results would be the same for women and older people.

Dr. Schoenfeld suspects that they should be.

“But obviously,” he says, “more studies are needed.”

Even now, though, the findings are encouraging and practical.

“It looks like 13 minutes in the gym can lead to significant improvements” in strength, he says. “That’s less than a fourth of someone’s lunch hour. Most of us can probably find that much time in our day.”

 

 

This article was originally published in The New York Times.  Read the original article.

This broken gene may have turned our ancestors into marathoners—and helped humans conquer the world

This broken gene may have turned our ancestors into marathoners—and helped humans conquer the world

Despite our couch potato lifestyles, long-distance running is in our genes. A new study in mice pinpoints how a stretch of DNA likely turned our ancestors into marathoners, giving us the endurance to conquer territory, evade predators, and eventually dominate the planet.

“This is very convincing evidence,” says Daniel Lieberman, a human evolutionary biologist at Harvard University who was not involved with the work. “It’s a nice piece of the puzzle about how humans came to be so successful.”

Human ancestors first distinguished themselves from other primates by their unusual way of hunting prey. Instead of depending on a quick spurt of energy—like a cheetah—they simply outlasted antelopes and other escaping animals, chasing them until they were too exhausted to keep running. This ability would have become especially useful as the climate changed 3 million years ago, and forested areas of Africa dried up and became savannas. Lieberman and others have identified skeletal changes that helped make such long-distance running possible, like longer legs. Others have also proposed that our ancestors’ loss of fur and expansion of sweat glands helped keep these runners cool.

Still, scientists don’t know much about the cellular changes that gave us better endurance, says Herman Pontzer, an evolutionary anthropologist at Duke University in Durham, North Carolina, who was not involved with the work.

Some clues came 20 years ago, when Ajit Varki, a physician-scientist at the University of California, San Diego (UCSD), and colleagues unearthed one of the first genetic differences between humans and chimps: a gene called CMP-Neu5Ac Hydroxylase (CMAH). Other primates have this gene, which helps build a sugar molecule called sialic acid that sits on cell surfaces. But humans have a broken version of CMAH, so they don’t make this sugar, the team reported. Since then, Varki has implicated sialic acid in inflammation and resistance to malaria.

In the new study, Varki’s team explored whether CMAH has any impact on muscles and running ability, in part because mice bred with a muscular dystrophy–like syndrome get worse when they don’t have this gene. UCSD graduate student Jonathan Okerblom put mice with a normal and broken version of CMAH (akin to the human version) on small treadmills. UCSD physiologist Ellen Breen closely examined their leg muscles before and after running different distances, some after 2 weeks and some after 1 month.

After training, the mice with the human version of the CMAH gene ran 12% faster and 20% longer than the other mice, the team reports today in the Proceedings of the Royal Society B. “Nike would pay a lot of money” for that kind of increase in performance in their sponsored athletes, Lieberman says.

The team discovered that the “humanized” mice had more tiny blood vessels branching into their leg muscles, and—even when isolated in a dish—the muscles kept contracting much longer than those from the other mice. The humanlike mouse muscles used oxygen more efficiently as well. But the researchers still have no idea how the sugar molecule affects endurance, as it serves many functions in a cell.

Similar improvements probably benefitted our human ancestors, says Andrew Best, a biological anthropology graduate student at the University of Massachusetts (UMass) in Amherst, who was not involved with the work. Varki’s team calculated that this genetic change happened 2 million to 3 million years ago, based on the genetic differences among primates and other animals.

That’s “slightly earlier than I’d have expected for such a large shift in [endurance],” says Best, as it predates some of the skeletal modifications, which don’t show up in the fossil record until much later. But to Pontzer, the date makes sense, as these ancestors needed endurance for walking and for digging up food. “Maybe it’s more than about running,” he notes.

However, “Mice are not humans or primates,” says Best’s adviser at UMass, Jason Kamilar, a biological anthropologist also not involved with the new work. “The genetic mechanisms in mice may not necessarily translate to humans or other primates.”

Either way, says Pontzer, the study is exciting because it gets researchers looking beyond fossils and into what might actually have gone on in the bodies of ancient animals. “This is really energizing work; it tells us how much is out there to do.”

 

 

This article was originally published in Science. Read the original article.