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Stay Hungry, Live Longer: the Science Behind the Calorie Restriction Diet

In a windowless, climate-controlled chamber on the third floor of the Dedman Life Sciences building at Southern Methodist University, thousands of fruit flies are on a diet so someday you won't have to be. The crumb-sized insects, weighing just 1 milligram each, live in slim glass and plastic tubes—100 flies...
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In a windowless, climate-controlled chamber on the third floor of the Dedman Life Sciences building at Southern Methodist University, thousands of fruit flies are on a diet so someday you won't have to be.

The crumb-sized insects, weighing just 1 milligram each, live in slim glass and plastic tubes—100 flies per—arranged in neat rows in 10 shallow cardboard boxes stacked on shelves, one on top of the other, like little fly condominiums.

The landlord of the flies is 37-year-old scientist Johannes Bauer, Ph.D. New to the biology department at SMU, an up-and-coming center for aging research, Bauer feeds his flies every other day with a mixture of sugar and yeast as he studies the effects of calorie restriction on the flies' health and longevity. In experiments he started at Brown University, he's found that consuming 30 to 50 percent fewer calories daily allows the Drosophila melanogaster fruit fly to live 10 to 40 percent longer than its natural lifespan—the equivalent in humans of living 120 years or more. Flies fed less are more alert, says Bauer. They're more active in almost every way, except they're not as fertile. Female flies share the tubes with males anyway because, says the scientist, "we want them to have some fun."

Semi-starvation doesn't sound like a party, but calorie restriction—a scientific term meaning under-nutrition without malnutrition—is now being touted as the latest fountain-of-youth secret for extending the human "health span" and possibly the life span. Gerontologists, oncologists, biochemists and biologists like Bauer, engaged in calorie restriction studies on lab animals, believe they've found an effective way to stave off cancers, heart disease, diabetes, arthritis, Alzheimer's and many other ailments. Staying hungry and living lean, say some researchers, is the only mechanism scientifically known to slow down the aging process and prevent age-related illnesses.

This comes as little surprise to children's book author Shannon Vyff, 33, of Round Rock. For the past eight years, she has been a member of the Calorie Restriction Society, a loosely connected (mostly through Facebook) international "community" devoted to austere eating for healthy purposes.

Vyff is now one of the society's most vocal supporters. She discovered calorie restriction after having three children in her 20s and hitting 200 pounds after the third. "I started searching online for diets and came across calorie restriction, and it made a lot of sense," says Vyff, 5-foot-10-inches and now 130 pounds, up from her lowest of 117. It took her just six months on CR to lose 85 pounds. "There was an adjustment period at first. But I started to like the foods that were healthy for me. The hardest thing was cutting out some of the things that I loved eating, like pasta and breads."

Calorie Restrictors—sometimes called CRONies, for Calorie Restriction/Optimal Nutrition—eat between 10 and 30 percent fewer calories than the typical adult, avoiding any foods high in fat, sugar or starch. Vyff now eats once a day, usually a lean chicken breast poached in water, some steamed broccoli or squash and maybe a glass of fresh orange juice. She eats red meat once every two weeks and prefers it cooked rare. Her daily calorie count hovers around 1,200 if she's not exercising; 1,600 to 1,800 if she runs 5 or 10 miles on the treadmill. She's also on a local roller derby team. When she's in training for that, she might help herself to a few extra morsels. Her favorite treat: six raw walnut halves and three Ghirardelli chocolate chips.

She credits CR with helping her pass her latest driving test without glasses for the first time. Her chronic knee pain disappeared, and her energy level zoomed, she says. Vyff's husband, Michael Trice, 32, also follows the CR plan, with occasional lapses for desserts shared with their kids. (CR is not recommended for children or teens, even if overweight.)

And do they think living on less food will let them live to be 100 or older? "Why not? If everyone started following calorie restriction, they could extend life by decades and be healthier in the middle years."

Adherents to calorie restriction and its cousins, raw foodism and veganism, tell similar stories about the positive effects, other than weight loss, of their eat-this/not-that regimens. They start to look younger than their years (something observed in calorie-restricted lab animals). Their chronic headaches, arthritis pain and sleep disorders go away without medication. They feel stronger, happier, more spiritually aware—as if a brain fog has lifted. Some report bursts of creative energy. Others describe a feeling of calm that envelops them after going with fewer calories for only a short time.

There is a scientific explanation for all of this. Reducing caloric intake, even by as little as 10 percent a day (skipping that extra helping of potatoes), sends the body's cells into a low level of stress that makes them strong when high stresses occur—much the way moderate stress caused by exercise improves people's health. "Restricting calories just a little bit puts your body in a state of stress, which makes you a little bit healthier," says Bauer.

More than 1,000 studies dating back 70 years have shown that eating less, a lot less, retards the aging process and boosts health in a wide variety of laboratory animals: fruit flies, spiders, nematodes, mice, rats, dogs and rhesus monkeys. Calorie-restricted monkeys, for instance, look less wrinkled as they age. They have less gray hair, and look and act younger than their regular-diet counterparts. Eating less seems to make the metabolic processes in the body work more efficiently, Bauer says. The body enters an altered state that puts the brakes on aging.

In mice, flies and monkeys, that is.

"Calorie restriction works in the lower organisms, we know," Bauer says. "But with humans it's anybody's guess so far."

The best guess in the scientific community is that starting a program of calorie restriction in your 30s might add two years, says Bauer. "If you start in your 40s, it's six months. Start later than that, it's negligible. It could be a few extra weeks."

Yet other researchers seriously doubt the health and longevity benefits of calorie restriction for humans. They say it affects fertility and sometimes causes brittle bones. Animals put on CR early in life are smaller in adulthood. Even devoted human followers of CR complain of cold hands and sniffles that never go away.

So why all the interest in calorie restriction now? What Bauer and other researchers know for sure is that there is a genetic component to the "calorie restriction response" in lab animals, including fruit flies, that is probably similar in humans. Given less food than the body thinks it needs, there is a "switch" that goes on, says Bauer, sending a message to the body's metabolic functions.

"If we could develop switches in the body to turn on and off the calorie restriction response, we could extend life expectancy," Bauer says. That's what he's looking for in his fruit flies—the "switch" in their genetic makeup that will give the order to their bodies to be healthy and live longer, no matter how much they eat.

And if they find the switch, says Bauer, scientists want to develop a drug that will activate that genetic on-off mechanism to mimic the health effects of calorie reduction without requiring a drastic change in diet. That will be the magic pill. One that fools the human body's metabolism and slows the aging process. One that allows people to remain disease-free without having to eat smaller meals.

And here's the good news: Some scientists think they've found it.

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It's called resveratrol. It's a natural substance available right now for a few cents a dose in health food and vitamin stores. Sold under various retail names, it's classified as a food supplement in the "antioxidant" category and is not regulated by the Food and Drug Administration.

It's been proven effective already on fat mice in a University of Pennsylvania study published in 2006 in the premier science journal Nature. Mice raised on the equivalent of a cheeseburger-and-fries diet were given resveratrol and compared to mice fattened without the supplement. The study found that the fat mice on resveratrol didn't lose weight but were healthier than the other mice. They also lived longer. In a French study, resveratrol-fed fat mice outran skinny ones in treadmill tests and built up healthy muscle even without exercise.

"Resveratrol could be the get-healthy drug," SMU's Bauer says. "It could be the miracle drug."

And Big Pharma doesn't even control it (yet). Medical and pharmaceutical interest in resveratrol has boomed over the past decade. Found naturally in certain vines, pine trees, red grapes, chocolate and peanuts, it is a chemical "polyphenol" that helps plants fight off drought, fungi, parasites and other external stressors. In the early 1990s, chemists looking to find the key to the "French paradox," which allows the French to eat fatty food without getting heart disease, zeroed in on resveratrol, part of the natural chemistry of red wine grapes and the likely reason red wine produced healthy heart effects.

Dozens of studies now have pinpointed the substance as a bonus not only to heart health but to the prevention of Alzheimer's and diabetes, reversals of inflammatory responses to spinal cord injuries, and the prevention and treatment of stroke. Resveratrol is being tested in clinical studies as a natural supplement to chemotherapy and has shown the ability to block cancer cells before they metastasize to bone.

In the most widely publicized report on resveratrol, researchers at Harvard Medical School showed that it mimicked calorie restriction and activated the "longevity gene" in yeast, extending its lifespan by 70 percent. Harvard professor David Sinclair, one of the scientists on that study, is so confident about the future of resveratrol, he founded a biomedical research company, Sirtris (named for the sirtuin family of enzymes that react to calorie restriction), which focuses on discovering resveratrol-like "small molecule drugs." Sirtris Pharmaceuticals was recently acquired by drug giant GlaxoSmithKline for $720 million.

Creating a synthetic resveratrol, one that can be approved by the FDA (and will be profitable for GlaxoSmithKline), will be one of the biggest medical discoveries since aspirin, Sinclair said in an interview on the PBS' NewsHour. "Let's admit that people have claimed that they've had the elixir of youth probably for the last 40,000 or more years. So I don't want to claim that we have the cure for aging, by any means, but it's really clear that modern medicine, modern molecular biology has finally grasped a potential way to manipulate lifespan and have a dramatic impact on health care."

A pill that diets for you is certainly easier than staying hungry. The question is how much resveratrol, or its derivatives, you'd have to take to get the benefits. In the concentrated version used in lab studies, each dose is about the equivalent of 14 bottles of red wine.

Paul McGlothin, 60, and wife Meredith Averill, 62, were subjects in several of the first controlled studies—at Harvard and at University of Washington in St. Louis—testing resveratrol's effects on people. "We're probably the most tested humans in the world," says McGlothin, CEO of an ad agency in Westchester, New York, and board chairman of the Calorie Restriction Society. After the studies, McGlothin and Averill decided to continue the calorie restriction regimen they started 15 years ago, without taking resveratrol—"though we think it's worth consideration," McGlothin says.

In their guidebook, The CR Way, the couple advises CRONies to eat 30 percent protein, 30 percent fat and 40 percent carbohydrates, focusing on making every bite as beneficial to the body as possible. No processed foods. Nothing fried, grilled or breaded. A day's worth of oatmeal, blueberries, lentils, poached salmon, barley broth, steamed sweet potatoes, fresh greens and other healthy vittles might add up to between 1,100 and 1,800 calories, depending on the person's height and weight.

By comparison, a typical adult American male under age 50 who's not on a restricted diet and leads a fairly sedentary life, eats about 2,500 calories a day without gaining weight. A typical female, about 2,000. For most Americans, too many calories come from high-fat, overprocessed food.

Rather than take resveratrol to be fat and healthy, McGlothin and Averill believe remaining underweight is the key to better health and feeling younger. McGlothin is 6 feet tall, weighs 133 pounds (down from 160 pounds 15 years ago) and has a 30-inch waist. He estimates that he consumes around 1,800 calories a day (the equivalent of one double-cheeseburger, large fries and a shake). Averill dropped 20 pounds after converting to calorie restriction and now weighs 110. Both say they haven't been sick in years.

Their eating day begins with the gradual intake of small meals, starting around 5 a.m. Their largest meal is breakfast, followed a few hours later by a lunch that might include raw or slightly steamed vegetables, beans, grains, fruit, fish and healthful fats. By 1 or 2 p.m., they're finished eating for the day. Fasting for 12 to 15 hours between "dinner" and breakfast, they believe, allows the digestive organs to rest.

"With CR, you feel more energetic, more than you ever dreamed possible," says McGlothin, who was featured with Averill in a recent 60 Minutes piece on CR, resveratrol and their effects on longevity. "You begin to just function better. My health was always average, not standout. But after CR, all my health markers began to be like that of a person 15 to 20 years younger."

McGlothin and Averill have worked closely with doctors, including Sinclair, to chart their progress as CR practitioners. "We're proving how it works," McGlothin says. "We're in this to accelerate research." And they like to boast that for many years now, they've been planning their 125th birthday parties.

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Back in the all-you-can-eat world, soaring obesity and inequality of health care are producing the first generation of Americans who may have a shorter life span than their parents.

After a century of increases in average life expectancy, America now ranks just above Mexico and most Eastern European nations for longevity, say statisticians at Boston College. Researchers at the University of Illinois in Chicago calculate that in the first half of this century, U.S. life expectancy will level off or get shorter.

In France, Switzerland and Japan, both men and women who live to age 65, are expected to live years longer on average than Americans who reach 65. It's estimated that 34 percent of American women currently are obese (typically, that is 20 percent over ideal weight), compared with just 4 percent in Japan. For men, it's 28 percent and 2 percent, respectively.

With obesity come related diseases such as diabetes, heart disease, kidney disease and cancer. By 2040, according to several studies, it's projected that two-thirds of all American adults will be obese or overweight. Childhood obesity is already at crisis levels, with dramatic increases in type 2 diabetes among the very young. As those overweight kids transition to overweight adults, mortality levels will spike as they fall victim to early heart attacks, strokes, kidney failure and other obesity-related ailments. Meanwhile, baby boomers who've gained a pound or two a year in every year of middle age will be lurching heavily and unhealthily into their late 60s and 70s.

"Definitely as you age, you need fewer calories," says Jo Ann Carson, Ph.D., who teaches clinical nutrition at University of Texas Southwestern Medical School and is a spokesperson for the American Dietetic Association. "Your metabolism slows down, requiring fewer calories to function. But those calories should come from better quality nutrients."

Carson offers a simple formula for calculating how much to decrease daily food consumption to reap the health benefits. For women, subtract 7 calories per day (from an average of 2,000) for every year past age 19. For men, it's 10 calories per day. Between ages 20 and 50, that's a gradual decrease of between 210 and 300 calories (the equivalent of a couple of slices of buttered toast).

Guidelines issued by the U.S. Department of Agriculture in 2005 (the next set of guidelines will be issued next year) also advise that Americans need to eat fewer calories, fats and carbs, and should add more fruits, vegetables and whole grains to their diets. Also recommended are 60 minutes of moderate-to-vigorous physical activity most days of the week.

Carson points to studies that show that calorie restriction followers have healthier glucose and insulin levels as they age, less incidence of inflammatory diseases and do better on cognitive function tests.

"There's something to this idea that getting just the right amount of calories for survival is an important way to manage health," she says. "They find that place where they eat just enough, somewhere between 1,300 and 1,500 calories a day. The body is remarkable in how it adjusts and tries to maintain a steady state to keep you alive and functioning."

The few calorie restriction studies using human subjects involved people voluntarily on the diet already, including one project at the Washington University School of Medicine looking at heart health among several groups, including 28 members of the Calorie Restriction Society who had been eating a CR diet for six years. The CR followers' hearts were more elastic and able to relax better between beats compared to subjects who ate a standard Western diet and did endurance exercise training. That study concluded that leanness helped prevent disease, but only calorie reduction slowed down aging.

The most recent short-term study on CR, conducted at the University of Munster in Germany and published online in January by the National Academy of Sciences, lasted three months and determined that reducing calorie intake by 30 percent improved memory ability by 20 percent in elderly individuals (average age 60.5 years).

Evidence keeps mounting showing the many positive effects of eating less. But is a lifetime of meager meals a guarantee of long life?

The skunk at the calorie restrictors' picnic is longevity expert Steven Austad, Ph.D., author of the book Why We Age and professor of biology at University of Texas Health Science Center at San Antonio. He doesn't believe that either CR or resveratrol will have as much of a "youthening" effect on humans as they do on lab animals. As he's told several conventions of the Calorie Restriction Society in the past, what works on flies and mice fails seven out of 10 times on people.

"We know that CR extends life in some animals, in some it doesn't," Austad says. "Some kinds of mice it works, some it doesn't. Some fruit flies it does, some it doesn't. People who study this tend to forget the experiments in which it didn't work."

Austad says he warns extreme calorie restrictors that "the jury is still out" on whether eating so little will add healthy years. "It might suppress the immune system and you could die from the next flu epidemic," he says. Or you could end up at 80 with muscles too weak to support even a thin body. "It would be extremely interesting and exciting if reducing your food intake would extend your life. But people in the aging community tend to jump on the bandwagon and make the leap from fruit flies to humans a little too enthusiastically."

And resveratrol? "Vastly overstated," Austad maintains. "Resveratrol has never been shown to extend life in any mammal except one—lab mice—eating so much fat that it was like you and I ate nothing but Big Macs every day. Other studies on mice eating a normal diet, resveratrol had no impact on how long they lived. It's an intriguing drug, but we don't have any evidence that it really does anything."

Nature and genetics play a much stronger role in longevity than diet, says Austad. In his research, he's interviewed dozens of people who lived to 100 or beyond. "The ranks of 100-year-olds are not populated by marathon runners," he says. "They didn't exercise. Some smoked for 95 years. They've got a genetic quirk."

Though he believes the first person to live to be 150 is already alive, Austad, 52, isn't hedging his own bets on the actuarial tables. He exercises "fairly fanatically" and doesn't smoke, but he also indulges in the occasional cocktail and he doesn't count calories.

"Here's an interesting thing—I've been to several meetings now of scientists who study calorie restriction, and I look around the room and don't see gaunt, skinny people," Austad says. "Some are slender, some are obese, some are muscular. If you look at those people who spend their lives [studying] CR, very few of them seem to do it themselves."

Back in the humid fruit fly chamber at SMU, Dr. Johannes Bauer laughs when asked if he practices calorie restriction. At 5-foot-7-inches, 140 pounds, the German-born scientist (who looks about 19) never exercises, doesn't take resveratrol and has never been on a diet. "Humans evolved as omnivores. They ate everything in their path," he says.

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Ben Franklin advised in Poor Richard's Almanac: "To lengthen thy life, lessen thy meals." Franklin lived into his 80s at a time when the average life expectancy for men was around 35. If he were around today, he might also advise eating more of thy meals raw.

At a recent potluck supper of the Our Heart of Dallas Radical Health Raw/Vegan Meetup, one of 10 raw food social groups in Dallas organized through Meetup.com, the dining table at host Amy Hirsch's apartment is crowded with uncooked edibles prepared by the 25 attendees (out of 237 members total). Shiny green chard leaves are wrapped around raw bits of cauliflower on one plate, and there's a container of pudding made from soaked hemp seeds and coconut milk. Fresh pineapple, blueberries, apples and other fruits brighten the spread. In the middle of the table sits a large bowl of something resembling wet hair. It's hijiki, a calcium-rich brown sea vegetable the "raw foodists," as they like to be called, eat like noodles.

Eating only uncooked, organic (as much as possible) plants and "super-foods" is the next step beyond simple calorie restriction. Pure raw foodists are vegans, eating no animal products at all, including dairy and eggs. Also no alcohol or caffeine. A raw foodist menu is made up mainly of uncooked vegetables and fruits, raw nuts and fresh juices. They too restrict their daily calorie count—sometimes to half that of a non-vegan's—because of the amount of leafy greens and other low-cal veggies they fill up on.

Miranda Martinez, a Dallas actress who also does theater production and PR, has been attending raw food get-togethers since converting to an all-raw vegan diet in 2007. A native of Panama, Martinez, now 36, had been a yoyo dieter and admitted "bread-aholic" for much of her life. She'd tried all the major fad and commercial weight-loss plans: Atkins, The Zone, Cybergenics, Weight Watchers, low-carb, high-protein and the Master Cleanse (a liquid fast involving lemonade, cayenne pepper and maple syrup). With most, she'd lose weight and then gain it all back and more, she recalls.

In December 2007, after hitting 205 pounds, the 5-foot-2-inch Martinez did a 30-day Master Cleanse fast, which knocked off 21 pounds, then started eating only organic raw fruits and vegetables, totaling about 1,500 calories a day. She lost eight pounds the first week on the raw foods and also lost her craving for sweets. Within a few months, her cholesterol levels dropped into healthy numbers. She began supplementing with so-called super-foods—spirulina, bee pollen, chia seeds, nutritional yeast and nori seaweed—and signed up for Bikram yoga classes three times a week.

By July 2008, Martinez had pared off 66 pounds, going from a size 20 to a size 4. She said it wasn't a struggle, and she is now such a believer in raw foods, she's started working as a "coach" to help those who want to try the raw way of life. She's also written an e-book full of tips and recipes, available on her Web site, VivaRaw.com.

"Before going raw, I felt a physical pull toward food," Martinez says. "I wanted the bread, the chips, the desserts. I had an emotional connection to food. For me, eating raw food has meant finding freedom. As long as my food is raw, I can eat and be satisfied. Now if I get hungry, I eat another apple. It's the best I've ever felt in my life. I don't get colds anymore. My allergies went away. This is my way of life now."

The raw foodists are energetic evangelists, touting the benefits they've reaped from giving up cooked and processed food. But there is no scientific basis, says UT-Southwestern nutrition expert Jo Ann Carson, for a raw food diet being healthier than one that includes cooked food, dairy and meats. "There is a science basis for calorie restriction," Carson says. "But raw foodists are an extreme."

Carson warns that an all-raw diet could lack adequate protein. "They're also losing some muscle, which makes them look thin," she says. "But when they get older, they're not going to have the muscle strength to support themselves easily. They could be more likely to fall over, break bones and die. [Going on raw foods] might keep them from getting cancer at 50, but if they live to be 80, their musculature is not going to be as good."

Isaac Clay, 28, is a stringbean at 6-foot-1-inch and 160 pounds. He met his girlfriend Courtney Taylor, 27, at a Dallas raw foodists' eat-and-greet last year. She started eating only raw vegan foods at age 20; he did at 23, after a period of depression and soul-searching following the sudden death of his mother contributed to his weight topping at 220. He credits going raw with his weight loss, his acne clearing and his chronic backaches going away. It also lifted him out of depression.

"Shock and grief derailed me," Clay recalls. "I stuffed myself with fast food two or three times a day. I would eat fried chicken feet at a Chinese restaurant. When I first got into raw foods, it was new and huge to me. Now it's second nature. Raw food makes the most sense." His two favorite items: a super-food supplement made of blue-green algae and a drink powder called Chocolate Bliss that can be blended with raw fruits or vegetables as a meal replacement.

Clay estimates there are about 600 hard-core raw foodists among the various Meetup groups in the Dallas area. Almost every weekend, there's a free buffet at somebody's house, where people share recipes and give testimonials about which foods are "supporting" them.

Being part of a community of like-minded eaters is as beneficial as the food itself, says Clay. "Getting together physically is a powerful thing. You can't just do it through the Internet. Life is all about relationships."

And his relationship with calorie-restricted raw foods has a higher goal: Living longer. "I just don't plan on dying," he says. "And as long as we're nourishing our cells properly, we're basically immortal."

On a diet of salads and seaweed, however, it might just feel like forever.

While working on this story, writer Elaine Liner started taking resveratrol daily and eating raw foods. She has lost 9 pounds.

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