Reviewed by Hansa D. Bhargava, MD on June 24, 2020
From the WebMD Archives

June 24, 2020 -- As a brain surgeon, neuroscientist, and father of three teenage boys, Rahul Jandial, 47, needs mental sharpness even more than most to get through his day. His strategy for achieving it is also unique.

He skips breakfast most days a week. And on Mondays and Thursdays, he eats only dinner.

"The brain is a hybrid vehicle and is in optimal function when it switches between sugar and fat as its fuel,” says Jandial, MD, an associate professor in the Division of Neurosurgery at Los Angeles-based City of Hope National Medical Center. “The easiest way to achieve this is with intermittent fasting.”

There are things to consider, he stresses, noting that the practice is not for everyone. But, according to mounting research, he may be on to something.

In addition to promoting weight loss, so-called intermittent fasting may deliver a host of other surprising health benefits, from improved heart and brain health, to a lower risk of diabetes, and even a longer life, recent research shows.

While much of the research has been in animals, promising human trials are emerging, and dozens more are underway.

And thanks to how-to books like The Fast Diet, Jandial’s Neurofitness: A Brain Surgeon’s secrets to Boost Performance and Unleash Creativity, and endorsements by celebrities like Twitter CEO Jack Dorsey (who eats only one meal a day), people are beginning to ask their doctors about it.

“The evidence that intermittent fasting benefits the health of overweight people is already very strong, and its potential to slow or reverse certain diseases looks very good,” says Mark Mattson, PhD, a neuroscientist at Johns Hopkins University in Baltimore and author of a new article on intermittent fasting in The New England Journal of Medicine.

Born to Fast

As Mattson notes, agriculture has been around for only 10,000 years or so. Before that, our ancestors not only had to go without food for long stretches, but had to hunt while hungry -- a task that requires mental and physical agility.

“From an evolutionary standpoint, we are genetically geared to function well in a food-deprived state,” he says.

Within as little as 12 hours of going without food, the body begins to make changes to conserve energy and operate more efficiently, explains Benjamin Horne, PhD, a clinical associate professor in the Division of Cardiovascular Medicine at Stanford University.

With its tank of glucose, or sugar, empty, it starts burning fat and producing chemical byproducts called ketones, which circulate throughout the body, improving insulin sensitivity, dampening inflammation, and feeding the brain. Blood levels of sodium and a compound called TMAO (implicated in heart disease) plummet, while red blood cell counts rise, providing a boost for heart health. And levels of a compound called brain-derived neurotrophic factor (BDNF), a protein essential for maintaining healthy neurons, spike.

Meanwhile, the cells move from building mode to rest and repair mode, cleaning up and fixing faulty mitochondria (the energy-producing furnaces of the cell), and reducing oxidative stress (the cell damage that makes tissue age).

Once we eat again, the cells have adapted to make better use of the fat, carbs, and proteins we throw at them.

“Switching back and forth between fasting and feeding has its own unique benefits,” says Mattson, noting that a strict calorie-restriction diet or a “ketogenic” or high-fat diet, would not have the same effects. “This is not a diet. It’s an eating pattern.”

Real Benefits, Real Risks

That eating pattern comes in several varieties.

Some plans call for restricting eating to a 6- to 12-hour window per day. Others call for eating normally a few days a week, then radically restricting calories for 2 or 3 days.

Both approaches have been shown to help, with studies in the realms of weight loss and metabolic health showing particular promise.

One recent 12-week study of overweight women in their 40s found that those who ate only 500 calories, 3 days per week, and did not restrict calories the other 4 days, lost just as much weight as those who cut calories to a strict 1,200 to 1,500 daily. And in a 6-month trial including 100 women, half were assigned to a 5:2 intermittent fasting plan (fasting 2 days and eating what they wanted the other 5) and the other half to a diet in which they cut daily calories by a quarter. The two groups lost the same amount of weight, but those in the 5:2 group lost more belly fat.

“It doesn’t necessarily provide an advantage for weight loss, but it works as well, and it provides another option for people,” says dietitian Felicia Lynn Steger, PhD, a nutrition science researcher at University of Alabama who has recommended fasting for patients who struggle with conventional diets.

Even in the absence of weight loss, fasting can help fend off diabetes and heart problems, studies suggest.

In one recent University of Alabama study, prediabetic men who limited their eating from 9 a.m. to 3 p.m. for 5 weeks, while still eating enough to maintain their weight, saw improved insulin sensitivity and blood pressure.

And studies of religious groups have shown that fasting as little as a day a month for the long term can affect heart health and longevity.

Horne, who’s also director of cardiovascular and genetic epidemiology at the Intermountain Heart Institute in Salt Lake City, started looking into fasting 20 years ago when he noticed something unique about his Utah patients. They had among the lowest heart disease death rates in the nation.

“We thought, there must be something in their lifestyle that is driving this,” he recalls, noting that about two-thirds of Utah residents are members of The Church of Jesus Christ of Latter-day Saints, or Mormon church, and most fast one Sunday per month. “Fasting really stuck out.”

Horne followed 2,000 patients for 4 years and found that the routine fasters were 45% less likely to die during the study period and 71% less likely to have heart failure. Those who had fasted most of their lives also generally lived longer.

Think Sharper, Live Longer

Perhaps the most intriguing but least researched benefit lies in brain health.

Scientists have known for decades that ketones, which are produced when the body is starved of carbohydrates and are able to penetrate the brain can be a potent energy source for brain cells and calm “electrical storms” or seizures in those who have a type of epilepsy. Fasting can also stimulate production of the anxiety-quelling neurotransmitter GABA. (During extreme fasting for the movie The Machinist, in which he lost 62 pounds, actor Christian Bale described it as “the most Zen-like state I’ve ever been in in my life.”) And animal studies have shown that intermittent fasting can prevent brain cell death, fend off Alzheimer’s-like symptoms, and boost the ability to learn and remember.

On the flip side, anyone who has ever felt like taking a nap after a big meal knows how too much food can sap mental energy.

But human studies looking at fasting and brain health have been slim to none, Mattson says.

“When it comes to disease treatment overall, there has been very little research done in humans yet.”

But dozens of studies are now underway, with researchers looking at the role fasting could potentially play in treating certain cancers, reducing side effects from chemotherapy, and addressing type 2 diabetes.

As the research unfolds, many are urging caution.

“There is a lot that we still do not know,” says Barbara Gordon, chair of the department of nutrition and dietetics at Idaho State University. “The most looming question is if this pattern of eating might have long-term detrimental health effects.”

Gordon is particularly leery of extreme diets, which require people to go whole days without eating and can lead to an “unhealthy pattern of bingeing and fasting.” And for people with diabetes, who take medicine to manage their blood sugar, fasting piled on top of the drugs can dip blood sugar to dangerous levels, she warns.

And for those who are already thin or elderly, fasting can potentially lead to bone loss and muscle wasting.

“We don’t want to let the hype get ahead of the evidence,” says Jandial, who would never recommend intermittent fasting to a cancer patient and urges anyone with a health condition to consult with their doctor before trying it.

But for people like himself, fortunate enough to be in good health and able to choose when and what to eat, he sees a few skipped meals as a small sacrifice for big gains.

“If I have the luxury to make small changes in the cadence of my eating that can give me an advantage in my focus, clarity, and health, why not?”

Show Sources

Rahul Jandial, MD, associate professor, Division of Neurosurgery, City of Hope National Medical Center, Los Angeles. “Twitter CEO Jack Dorsey: ‘I eat seven meals every week, just dinner.’”

Mark Mattson, PhD, neuroscientist, Johns Hopkins University, Baltimore.

Benjamin Horne, PhD, clinical associate professor, Division of Cardiovascular Medicine, Stanford University; director, cardiovascular and genetic epidemiology, Intermountain Heart Institute, Salt Lake City.

Nutrients: “Pilot Study of Novel Intermittent Fasting Effects on Metabolomic and Trimethylamine N-oxide Changes During 24-hour Water-Only Fasting in the FEELGOOD Trial.”

Felicia Lynn Steger, PhD, nutrition science researcher, University of Alabama, Birmingham.

Circulation: “Abstract 11123: Intermittent Fasting Lifestyle and Human Longevity in Cardiac Catheterization Populations.” “Christian Bale on What It Felt Like to Lose So Much Weight for His Role in The Machinist.”

Pediatric Neurology: “The Neuropharmacology of the Ketogenic Diet.”

Barbara Gordon, chair, department of nutrition and dietetics, Idaho State University, Pocatello.

American Heart Association: “Regular fasting could lead to longer, healthier life.”

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