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Why When You Eat Might Be as Important as What You Eat

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Fasting and eating schedule
Adapted from Wilkinson MJ, Cell Metab, 2019

About 1 in 3 American adults have metabolic syndrome, a group of early warning signs for increased risk of type 2 diabetes, heart disease, and stroke. To help avoid such health problems, these folks are often advised to pay close attention to the amount and type of foods they eat. And now it seems there may be something else to watch: how food intake is spaced over a 24-hour period.

In a three-month pilot study, NIH-funded researchers found that when individuals with metabolic syndrome consumed all of their usual daily diet within 10 hours—rather than a more customary span of about 14 hours—their early warning signs improved. Not only was a longer stretch of daily fasting associated with moderate weight loss, in some cases, it was also tied to lower blood pressure, lower blood glucose levels, and other improvements in metabolic syndrome.

The study, published in Cell Metabolism, is the result of a joint effort by Satchidananda Panda, Salk Institute for Biological Sciences, La Jolla, CA, and Pam R. Taub, University of California, San Diego [1]. It was inspired by Panda’s earlier mouse studies involving an emerging dietary intervention, called time-restricted eating (TRE), which attempts to establish a consistent daily cycle of feeding and fasting to create more stable rhythms for the body’s own biological clock [2, 3].

But would observations in mice hold true for humans? To find out, Panda joined forces with Taub, a cardiologist and physician-scientist. The researchers enlisted 19 men and women with metabolic syndrome, defined as having three or more of five specific risk factors: high fasting blood glucose, high blood pressure, high triglyceride levels, low “good” cholesterol, and/or extra abdominal fat. Most participants were obese and taking at least one medication to help manage their metabolic risk factors.

In the study, participants followed one rule: eat anything that you want, just do so over a 10-hour period of your own choosing. So, for the next three months, these folks logged their eating times and tracked their sleep using a special phone app created by the research team. They also wore activity and glucose monitors.

By the pilot study’s end, participants following the 10-hour limitation had lost on average 3 percent of their weight and about 3 percent of their abdominal fat. They also lowered their cholesterol and blood pressure. Although this study did not find 10-hour TRE significantly reduced blood glucose levels in all participants, those with elevated fasting blood glucose did have improvement. In addition, participants reported other lifestyle improvements, including better sleep.

The participants generally saw their metabolic health improve without skipping meals. Most chose to delay breakfast, waiting about two hours after they got up in the morning. They also ate dinner earlier, about three hours before going to bed—and then did no late night snacking.

After the study, more than two-thirds reported that they stuck with the 10-hour eating plan at least part-time for up to a year. Some participants were able to cut back or stop taking cholesterol and/or blood-pressure-lowering medications.

Following up on the findings of this small study, Taub will launch a larger NIH-supported clinical trial involving 100 people with metabolic syndrome. Panda is now exploring in greater detail the underlying biology of the metabolic benefits observed in the mice following TRE.

For people looking to improve their metabolic health, it’s a good idea to consult with a doctor before making significant changes to one’s eating habits. But the initial data from this study indicate that, in addition to exercising and limiting portion size, it might also pay to watch the clock.

References:

[1] Ten-hour time-restricted eating reduces weight, blood pressure, and atherogenic lipids in patients with metabolic syndrome. Wilkinson MJ, Manoogian ENC, Zadourian A, Lo H, Fakhouri S, Shoghi A, Wang X, Fleisher JG, Panda S, Taub PR. Cell Metab. 2019 Jan 7; 31: 1-13. Epub 2019 Dec 5.

[2] Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Hatori M, Vollmers C, Zarrinpar A, DiTacchio L, Bushong EA, Gill S, Leblanc M, Chaix A, Joens M, Fitzpatrick JA, Ellisman MH, Panda S. Cell Metab. 2012 Jun 6;15(6):848-60.

[3] Time-restricted feeding is a preventative and therapeutic intervention against diverse nutritional challenges. Chaix A, Zarrinpar A, Miu P, Panda S. Cell Metab. 2014 Dec 2;20(6):991-1005.

Links:

Metabolic Syndrome (National Heart, Lung, and Blood Institute/NIH)

Obesity (National Institute of Diabetes and Digestive and Kidney Diseases/NIH)

Body Weight Planner (NIDDK/NIH)

Satchidananda Panda (Salk Institute for Biological Sciences, La Jolla, CA)

Taub Research Group (University of California, San Diego)

NIH Support: National Institute of Diabetes and Digestive and Kidney Diseases


Creative Minds: Designing Personalized Clinical Trials

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Karina Davidson

Karina Davidson/Jörg Meyer

It might have been 25 years ago, but Karina Davidson remembers that day like yesterday. She was an intern in clinical psychology, and two concerned parents walked into the hospital with their troubled, seven-year-old son. The boy was severely underweight at just 37 pounds and had been acting out violently toward himself and others. It seemed as though Ritalin, a drug commonly prescribed for Attention Deficit Disorder, might help. But would it?

To find out, the clinical team did something unconventional: they designed for the boy a clinical trial to test the benefit of Ritalin versus a placebo. The boy was randomly assigned to take either the drug or placebo each day for four weeks. As a controlled study, neither clinical staff nor the family knew whether he was taking the drug or placebo at any given time. The result: Ritalin wasn’t the answer. The boy was spared any side effects from long term administration of a medication that wouldn’t help him, and his doctors could turn to other potentially more beneficial approaches to his treatment.

Davidson, now an established clinical psychologist at the Columbia University Irving Medical Center, New York, wants to take the unconventional approach that helped this boy and make it more of the norm in medicine. With support from a 2017 NIH Director’s Transformative Research Award, she and her colleagues will develop three pilot computer applications—or digital platforms—to help doctors conduct one-person studies in their offices.


Muscle Enzyme Explains Weight Gain in Middle Age

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Woman weighing herself

Thinkstock/tetmc

The struggle to maintain a healthy weight is a lifelong challenge for many of us. In fact, the average American packs on an extra 30 pounds from early adulthood to age 50. What’s responsible for this tendency toward middle-age spread? For most of us, too many calories and too little exercise definitely play a role. But now comes word that another reason may lie in a strong—and previously unknown—biochemical mechanism related to the normal aging process.

An NIH-led team recently discovered that the normal process of aging causes levels of an enzyme called DNA-PK to rise in animals as they approach middle age. While the enzyme is known for its role in DNA repair, their studies show it also slows down metabolism, making it more difficult to burn fat. To see if reducing DNA-PK levels might rev up the metabolism, the researchers turned to middle-aged mice. They found that a drug-like compound that blocked DNA-PK activity cut weight gain in the mice by a whopping 40 percent!


Obesity Research: Study Shows Significant Benefits of Modest Weight Loss

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5% weight lossFor the one in three American adults who are obese, recommendations to lose substantial amounts of weight through a combination of diet and exercise can seem daunting and, at times, hopeless. But a new study should come as encouraging news for all those struggling to lose the extra pounds: even a modest goal of 5 percent weight loss delivers considerable health benefits.

In the NIH-funded study, people with obesity who lost just 5 percent of their body weight—about 12 pounds on average—showed improvements in several risk factors for type 2 diabetes and heart disease. They also showed metabolic improvements in many parts of the body, including the liver, pancreas, muscle, and fat tissue. While people who lost additional weight enjoyed further improvements in their health, the findings reported in the journal Cell Metabolism show that sometimes it really does pay to start small [1].


Flipping a Genetic Switch on Obesity?

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Illustration of a DNA switchWhen weight loss is the goal, the equation seems simple enough: consume fewer calories and burn more of them exercising. But for some people, losing and keeping off the weight is much more difficult for reasons that can include a genetic component. While there are rare genetic causes of extreme obesity, the strongest common genetic contributor discovered so far is a variant found in an intron of the FTO gene. Variations in this untranslated region of the gene have been tied to differences in body mass and a risk of obesity [1]. For the one in six people of European descent born with two copies of the risk variant, the consequence is carrying around an average of an extra 7 pounds [2].

Now, NIH-funded researchers reporting in The New England Journal of Medicine [3] have figured out how this gene influences body weight. The answer is not, as many had suspected, in regions of the brain that control appetite, but in the progenitor cells that produce white and beige fat. The researchers found that the risk variant is part of a larger genetic circuit that determines whether our bodies burn or store fat. This discovery may yield new approaches to intervene in obesity with treatments designed to change the way fat cells handle calories.


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